The conversion bile salts to sulfate derivatives has been shown to be a major pathway for elimination of bile salts in chronic cholestatic liver disease. We are investigating the production and renal clearance of bile salt sulfates in infants and children with cholestasis due to biliary malformations and parenchymal disease. Studies concerning the role of nutrition in bilirubin metabolism are in progress. The differential effects of carbohydrate, amino acid and lipid intake on fasting hyperbilirubinemia are under investigation. We are especially interested in the mechanism whereby serum bilirubin rises and falls with fasting and refeeding, respectively. The regulation of fibrinogen synthesis and renewal during early development, and under conditions of stress is being investigated. The effects of free fatty acids on fibrinogen production in animals and in liver slices will be studied with appropriate isotopic precursors. The interaction between the serum growth factor glycyl-histidyl-lysine (GHL) and liver cell surfaces, and the effect of GHL on the action of somatomedin will be further investigated. In addition, fibrin-like surface proteins in normal and transformed liver cells will be isolated and characterized in order to study their role in cellular adhesiveness and monolayer formation. BIBLIOGRAPHIC REFERENCES: Pickart, L. R. and Thaler, M. M. Free Fatty acids and albumin as mediators of thrombin-stimulated fibrinogen synthesis. Am. J. Physiol. (April, 1976), in press. Thaler, M. M. Regulation of perinatal bilirubin metabolism In Macy Symposia, 1976 ( in press).